LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells

Gary LeRoy, Ozgur Oksuz, Nicolas Descostes, Yuki Aoi, Rais A. Ganai, Havva Ortabozkoyun Kara, Jia Ray Yu, Chul Hwan Lee, James Stafford, Ali Shilatifard, Danny Reinberg*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

FACT (facilitates chromatin transcription) is a protein complex that allows RNA polymerase II (RNAPII) to overcome the nucleosome-induced barrier to transcription. While abundant in undifferentiated cells and many cancers, FACT is not abundant or is absent in most tissues. Therefore, we screened for additional proteins that might replace FACT upon differentiation. We identified two proteins, lens epithelium-derived growth factor (LEDGF) and hepatoma-derived growth factor 2 (HDGF2), each containing two high mobility group A (HMGA)–like AT-hooks and a methyl-lysine reading Pro-Trp-Trp-Pro (PWWP) domain that binds to H3K36me2 and H3K36me3.LEDGF and HDGF2 colocalize with H3K36me2/3 at genomic regions containing active genes. In myoblasts, LEDGF and HDGF2 are enriched on most active genes. Upon differentiation to myotubes, LEDGF levels decrease, while HDGF2 levels are maintained. Moreover, HDGF2 is required for their proper expression. HDGF2 knockout myoblasts exhibit an accumulation of paused RNAPII within the transcribed region of many HDGF2 target genes, indicating a defect in early elongation.

Original languageEnglish (US)
Article numbereaay3068
JournalScience Advances
Volume5
Issue number10
DOIs
StatePublished - Oct 2 2019

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epithelium
lenses
cells
chromatin
genes
proteins
hooks
lysine
elongation
cancer

ASJC Scopus subject areas

  • Physics and Astronomy (miscellaneous)
  • General

Cite this

LeRoy, G., Oksuz, O., Descostes, N., Aoi, Y., Ganai, R. A., Kara, H. O., ... Reinberg, D. (2019). LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells. Science Advances, 5(10), [eaay3068]. https://doi.org/10.1126/sciadv.aay3068
LeRoy, Gary ; Oksuz, Ozgur ; Descostes, Nicolas ; Aoi, Yuki ; Ganai, Rais A. ; Kara, Havva Ortabozkoyun ; Yu, Jia Ray ; Lee, Chul Hwan ; Stafford, James ; Shilatifard, Ali ; Reinberg, Danny. / LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells. In: Science Advances. 2019 ; Vol. 5, No. 10.
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abstract = "FACT (facilitates chromatin transcription) is a protein complex that allows RNA polymerase II (RNAPII) to overcome the nucleosome-induced barrier to transcription. While abundant in undifferentiated cells and many cancers, FACT is not abundant or is absent in most tissues. Therefore, we screened for additional proteins that might replace FACT upon differentiation. We identified two proteins, lens epithelium-derived growth factor (LEDGF) and hepatoma-derived growth factor 2 (HDGF2), each containing two high mobility group A (HMGA)–like AT-hooks and a methyl-lysine reading Pro-Trp-Trp-Pro (PWWP) domain that binds to H3K36me2 and H3K36me3.LEDGF and HDGF2 colocalize with H3K36me2/3 at genomic regions containing active genes. In myoblasts, LEDGF and HDGF2 are enriched on most active genes. Upon differentiation to myotubes, LEDGF levels decrease, while HDGF2 levels are maintained. Moreover, HDGF2 is required for their proper expression. HDGF2 knockout myoblasts exhibit an accumulation of paused RNAPII within the transcribed region of many HDGF2 target genes, indicating a defect in early elongation.",
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LeRoy, G, Oksuz, O, Descostes, N, Aoi, Y, Ganai, RA, Kara, HO, Yu, JR, Lee, CH, Stafford, J, Shilatifard, A & Reinberg, D 2019, 'LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells', Science Advances, vol. 5, no. 10, eaay3068. https://doi.org/10.1126/sciadv.aay3068

LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells. / LeRoy, Gary; Oksuz, Ozgur; Descostes, Nicolas; Aoi, Yuki; Ganai, Rais A.; Kara, Havva Ortabozkoyun; Yu, Jia Ray; Lee, Chul Hwan; Stafford, James; Shilatifard, Ali; Reinberg, Danny.

In: Science Advances, Vol. 5, No. 10, eaay3068, 02.10.2019.

Research output: Contribution to journalArticle

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T1 - LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells

AU - LeRoy, Gary

AU - Oksuz, Ozgur

AU - Descostes, Nicolas

AU - Aoi, Yuki

AU - Ganai, Rais A.

AU - Kara, Havva Ortabozkoyun

AU - Yu, Jia Ray

AU - Lee, Chul Hwan

AU - Stafford, James

AU - Shilatifard, Ali

AU - Reinberg, Danny

PY - 2019/10/2

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N2 - FACT (facilitates chromatin transcription) is a protein complex that allows RNA polymerase II (RNAPII) to overcome the nucleosome-induced barrier to transcription. While abundant in undifferentiated cells and many cancers, FACT is not abundant or is absent in most tissues. Therefore, we screened for additional proteins that might replace FACT upon differentiation. We identified two proteins, lens epithelium-derived growth factor (LEDGF) and hepatoma-derived growth factor 2 (HDGF2), each containing two high mobility group A (HMGA)–like AT-hooks and a methyl-lysine reading Pro-Trp-Trp-Pro (PWWP) domain that binds to H3K36me2 and H3K36me3.LEDGF and HDGF2 colocalize with H3K36me2/3 at genomic regions containing active genes. In myoblasts, LEDGF and HDGF2 are enriched on most active genes. Upon differentiation to myotubes, LEDGF levels decrease, while HDGF2 levels are maintained. Moreover, HDGF2 is required for their proper expression. HDGF2 knockout myoblasts exhibit an accumulation of paused RNAPII within the transcribed region of many HDGF2 target genes, indicating a defect in early elongation.

AB - FACT (facilitates chromatin transcription) is a protein complex that allows RNA polymerase II (RNAPII) to overcome the nucleosome-induced barrier to transcription. While abundant in undifferentiated cells and many cancers, FACT is not abundant or is absent in most tissues. Therefore, we screened for additional proteins that might replace FACT upon differentiation. We identified two proteins, lens epithelium-derived growth factor (LEDGF) and hepatoma-derived growth factor 2 (HDGF2), each containing two high mobility group A (HMGA)–like AT-hooks and a methyl-lysine reading Pro-Trp-Trp-Pro (PWWP) domain that binds to H3K36me2 and H3K36me3.LEDGF and HDGF2 colocalize with H3K36me2/3 at genomic regions containing active genes. In myoblasts, LEDGF and HDGF2 are enriched on most active genes. Upon differentiation to myotubes, LEDGF levels decrease, while HDGF2 levels are maintained. Moreover, HDGF2 is required for their proper expression. HDGF2 knockout myoblasts exhibit an accumulation of paused RNAPII within the transcribed region of many HDGF2 target genes, indicating a defect in early elongation.

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